川芎嗪对CIA大鼠足爪组织MMP-13蛋白表达及血清VEGF、IL-17和IL-23水平的影响

 目的： 探讨川芎嗪（tetramethylpyrazine，TMP)治疗胶原性关节炎（collagen-induced arthritis，CIA）大鼠的可能机制。方法：采用Ⅱ型胶原诱导CIA大鼠模型。随机分为正常对照组、模型组与药物处理组，用免疫组化染色法和Western blotting分析检测足爪组织中基质金属蛋白酶（MMP）-13蛋白的表达；HE染色观察不同剂量的TMP对CIA大鼠足爪组织病理学变化的影响；ELISA法检测CIA大鼠血清中VEGF、IL-17和IL-23的含量。结果：与CIA组相比，CIA+TMP (100 mg·kg-1)组大鼠体重明显回升（P<0.01）,足爪组织胞浆中MMP-13蛋白表达降低了31.82%（P<0.01），大鼠足爪皮下组织病理改变明显减轻，血清中VEGF、IL-17和IL-23的含量分别降低了33.33%、27.40%和33.33%（P<0.01）。结论：TMP(100 mg·kg-1)对CIA大鼠炎症有明显的抑制作用，其机制可能与其下调MMP-13蛋白表达，抑制炎症细胞浸润及血管增生，降低VEGF、IL-17和IL-23的产生有关。

Effect of tetramethylpyrazine on paw MMP-13 protein expression and serum VEGF, IL-17 and IL-23 levels in rats with collagen-induced arthritis

AIM：To investigate the mechanism of tetramethylpyrazine (TMP) in treating collagen-induced arthritis (CIA) in rats. METHODS：The rat model of type II collagen-induced arthritis was established and the rats were randomly divided into normal control group, CIA group and TMP treatment group. The protein expression of matrix metalloproteinase 13 (MMP-13) in paw tissues was detected by immunohistochemical staining and Western blotting. The histopathological changes of the skin in the rat paws were observed with HE staining. The levels of vascular endothelial growth factor (VEGF), interleukin 17 (IL-17) and interleukin 23 (IL-23) in the serum of CIA rats were detected by ELISA. RESULTS：Compared with CIA group, TMP at a dose of 100 mg/kg significantly reduced the weight loss in CIA rats and decreased the protein expression of MMP-13 by 31.82%. TMP also attenuated the pathological changes of the paw subcutaneous tissues. TMP obviously decreased the levels of VEGF by 33.33%, IL-17 by 27.40% and IL-23 by 33.33% in the serum. CONCLUSION：TMP significantly inhibits the development of CIA by decreasing the protein expression of MMP-13, inhibiting the inflammatory cell infiltration and vascular proliferation, and reducing the production of VEGF, IL-17 and IL-23 in CIA rats.